19-35765048-C-G

Variant names:

• chr19-35765048-C-G
• rs1369860889
• NM_001367856.1:c.641C>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001367856.1(PROSER3):​c.641C>G​(p.Ser214Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000687 in 1,455,566 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/19 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S214F) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: PROSER3 NM_001367856.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.100
• Publications: 0 publications found

Genes affected

PROSER3 (HGNC:25204): (proline and serine rich 3)

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.20564404).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001367856.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PROSER3	NM_001367856.1	MANE Select	c.641C>G	p.Ser214Cys	missense	Exon 7 of 11	NP_001354785.1	A0A2R8Y8D9
	PROSER3	NM_001438802.1		c.638C>G	p.Ser213Cys	missense	Exon 7 of 11	NP_001425731.1
	PROSER3	NM_001395458.1		c.641C>G	p.Ser214Cys	missense	Exon 7 of 12	NP_001382387.1	A0A2R8Y8D9

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PROSER3	ENST00000646935.2	MANE Select	c.641C>G	p.Ser214Cys	missense	Exon 7 of 11	ENSP00000496769.2	A0A2R8Y8D9
	PROSER3	ENST00000396908.10	TSL:1	c.641C>G	p.Ser214Cys	missense	Exon 7 of 11	ENSP00000380116.5
	PROSER3	ENST00000696041.1		c.641C>G	p.Ser214Cys	missense	Exon 7 of 11	ENSP00000512346.1	A0A8Q3WKY3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.87e-7 AC: 1 AN: 1455566 Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1 AN XY: 724274

African (AFR) AF: 0.00 AC: 0 AN: 33368

American (AMR) AF: 0.00 AC: 0 AN: 44654

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26098

East Asian (EAS) AF: 0.00 AC: 0 AN: 39628

South Asian (SAS) AF: 0.00 AC: 0 AN: 86082

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52406

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5754

European-Non Finnish (NFE) AF: 9.03e-7 AC: 1 AN: 1107408

Other (OTH) AF: 0.00 AC: 0 AN: 60168

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.17	T
BayesDel_noAF	Benign	-0.48
CADD	Benign	22
DANN	Uncertain	0.99
DEOGEN2	Benign	0.034	T
Eigen	Benign	0.14
Eigen_PC	Benign	0.027
FATHMM_MKL	Benign	0.66	D
LIST_S2	Benign	0.72	T
M_CAP	Benign	0.017	T
MetaRNN	Benign	0.21	T
MetaSVM	Benign	-0.98	T
PhyloP100		-0.10
PROVEAN	Benign	-1.4	N
REVEL	Benign	0.074
Sift	Uncertain	0.027	D
Sift4G	Uncertain	0.022	D
Vest4		0.21
MutPred		0.23		Loss of phosphorylation at S214 (P = 0.0012)
MVP		0.42
ClinPred		0.47	T
GERP RS		2.5
Varity_R		0.086
gMVP		0.089
Mutation Taster		=91/9	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs1369860889; hg19: chr19-36255949;